Compound May Enhance Muscle Repair in Aging Individuals

Scientists have identified a sulfur-based compound that could enhance the body's natural muscle repair mechanisms. This compound, lipoic acid trisulfide (LASSS), appears to protect and strengthen hepatocyte growth factor (HGF), a key protein in muscle regeneration. The discovery may lead to new methods for combating muscle loss and preserving strength in older adults.

Skeletal muscle often deteriorates with age. This process can cause strength loss, increased scarring, and a reduction in fast-twitch muscle fibers. Researchers at Kyushu University, led by Professor Ryuichi Tatsumi, published their findings in *Scientific Reports*.

HGF is essential for initiating skeletal muscle repair. It remains inactive until muscle tissue is injured or mechanically stimulated. Once released, HGF binds to c-met receptors on satellite cells, which are stem cells responsible for muscle maintenance and repair. This binding activates the satellite cells, allowing them to multiply, mature, and rebuild damaged muscle fibers.

Aging can impair this repair system. Previous research indicated that HGF can undergo nitration, a chemical modification that adds a nitro group to specific sites on the protein. These sites are crucial for HGF to bind with c-met. Nitrated HGF cannot effectively attach to its receptor, hindering muscle repair. This functional loss may contribute to muscle wasting and reduced regeneration in older individuals.

The research team investigated two antioxidant compounds, glutathione trisulfide (GSSSG) and LASSS. Both are trisulfides, molecules containing three sulfur atoms. Initial experiments showed both compounds reduced HGF nitration. However, neither fully restored the protein's ability to bind to its receptor. When the researchers increased the concentration of LASSS, HGF's binding ability more than doubled compared to untreated HGF. It also became more resistant to nitration-induced functional loss. This effect was unique to LASSS; GSSSG did not produce the same result.

These findings suggest that LASSS may directly alter HGF's structure, creating an enhanced form that binds more strongly to its receptor and resists chemical damage. The team also tested LASSS in mice with muscle atrophy. Mice treated with LASSS showed significantly lower levels of nitration. This indicates that LASSS's protective effects extend beyond laboratory settings. Further studies with aging animals are needed to confirm its safety and effectiveness in living organisms. This research offers a potential strategy for maintaining muscle repair during aging and periods of inactivity.